Extrapulmonary TB in North Eastern Nigeria: A 10-Year Retrospective Review

Background: Information on extrapulmonary TB is scarce in Nigeria despite being one of the 22 countries with highest burden of tuberculosis in the world and the most populous country in sub-Saharan Africa where the dual epidemics of TB and HIV/AIDS mutually co-exist. Objective: The purpose of this study was to document the burden of extrapulmonary TB in North-eastern Nigeria. Methodology: A retrospective cross-sectional study was conducted at a DOTS treatment centre in a tertiary hospital in North-eastern Nigeria. TB treatment registers and case records of 1240 patients were reviewed over a 10-year period. Results: Out of the 1240 TB cases who received treatment at the facility; 179 (14.4%) had extra-pulmonary TB. Skeletal TB and TB lymphadenitis were the predominant forms of extra-pulmonary TB in the study i.e. 51 (28.5%) and 50 (28.0%), respectively. This was closely followed by abdominal TB (38 (21.2%), tuberculous pleural effusion (23 (12.8%), miliary TB (9 (5.0%), TB meningitis (3 (1.7%) and others (5 (2.8%): viz; 1 (0.6%) each ofTB of the breast, TB of the skin, adrenal TB, genitourinary TB and TB pericarditis respectively. Only 101 (56.4%) of the study subjects had information on their HIV status; of whom 52 (51.5%) were HIV positive and 49 (48.5%) HIV negative. Conclusion: The study has shown that extrapulmonary TB was relatively common among TB patients receiving care at the facility despite its diagnostic challenges particularly in a resource poor setting like ours.


Introduction
Tuberculosis (TB) is a global public health issue [1,2]. Despite the recent advances in diagnosis, management and the implementation of the Stop TB programme, TB (especially in the presence of HIV) continues to pose great of challenges in developing countries of sub Saharan Africa and Asia [3] Recently WHO ranked sub Saharan Africa second after South-east Asia on region affected by high burden of TB [4]. Among

Journal Of Prevention & Infection Control 2471-9668
African countries, Nigeria is ranked second after South Africa with high prevalence of TB [4]. Between 1990 and 2007, the annual incidence rate of TB has increased remarkably in Nigeria from about 174 to 352 per 100,000 populations [5]. In 2013, Nigeria had an estimated annual incidence rate of 338 cases per 100,000 populations and this Figure 1 is above the average annual TB incidence rate in the entire sub Saharan Africa [6].
Primarily, TB infection affects the lung (pulmonary TB) but few cases may occur outside the lung (extra-pulmonary TB (EPTB)), in areas such as the lymph nodes, meninges, spine, joints, central nervous system, and gastrointestinal system with wide range of clinical presentation [7]. Thus, EPTB requires high index of clinical suspicion for its diagnosis [1]. High prevalence of EPTB has been identified in recent times due to the HIV/ AIDS epidemic particularly in sub Saharan Africa [8]. Reported prevalence of EPTB varies according to region and patient subgroups. In India for example, studies have shown that extrapulmonary TB constitute about 10-15% of all forms of TB. In a recent review Zumla and colleagues have reported that EPTB occurs in 10-42% of TB patients depending on the region, ethnic background, age, underlying disease, immune status of the patient as well as genotype of the Mycobacterium tuberculosis strain [3]. Presence of coexisting HIV infection has been shown to increase the incidence of EPTP to as much as 62% [9]. In 2010, the prevalence of HIV infection in Nigeria is estimated around 3.4%, therefore, opportunistic infection such EPTB may continue to pose challenges among the HIV-infected population [9]. However, there is paucity of data EPTB in Nigeria and none from the Northeastern part of the country. Therefore the study was aimed to assess the burden of EPTB at a DOTS treatment centre, Northeastern Nigeria. The commonest form of EPTB from the study were skeletal TB (51 (28.5%) and TB lymphadenitis 50 (28.0%), this was closely followed by abdominal tuberculosis 38 (21.2%), tuberculous pleural effusion 23 (12.8%), miliary TB (9 (5.0%), TB meningitis 3 (1.7%) and others 5 (2.8%); which include 1 (0.6%) each of; TB of the breast, TB of the skin, adrenal TB, genitourinary TB and TB pericarditis respectively (Figure 1). TB of the spine (that is, Pott's disease) was the commonest form of skeletal TB in the study i.e. 49 (96.1%) while TB osteoarthritis constituted the remaining 2 (3.9%). Information on HIV status was available for 101 (56.4%) patients; out of these 49 (48.5%) were HIV negative and 52 (51.8%) HIV positive ( Table 1). TB lymphadenitis, TB pleural effusion and military TB were common among HIV positive subjects in the study than HIV negatives.

Discussion
Overall, EPTB represents 14.4% of all TB cases in this study. This figure favourably compares with those reported in similar studies for example; in a 13-year epidemiologic study in the USA a prevalence of 18.7% was reported [8], while in India the burden of extra-pulmonary TB among all TB cases was reported to be between 10-15% [10]. In a retrospective cohort study by Ade et al in Bénin republic reported an EPTB rate of 9% [11]. However, this rate was considerable lower when compared with rates reported in a similar study in Ethiopia (32%) [12].
This current study also shows that the prevalence of EPTB is lower among HIV seropositive patients (48.5%) and this finding is not consistent with the result von Ryon et al who reported 55% cases EPTB among HIV/AIDS patients [13] ( Table 2). The disparity in prevalence rates reported by these studies may be explained by variation in epidemiologic risk factors for TB, variation in study populations, differences in study design, as well as variation in diagnostic tools for the detection EPTB and strain differences in mycobacterium TB genotypes.

Journal Of Prevention & Infection Control 2471-9668
The predominant forms of extra-pulmonary TB in the study were skeletal TB and TB lymphadenitis followed by abdominal TB and tuberculous pleural effusion. This finding is tandem with other studies [14][15][16]. In addition, TB lymphadenitis and pleural effusion were common among HIV positive patients than HIV-negatives. This may be as a result of immune reconstitution following the commencement of anti-retroviral drugs in the presence of TB infection or as a result of the HIV infection itself as shown by several studies [17][18][19]. Furthermore the commonest form of skeletal TB in the study was spinal TB (i.e., Pott's disease); this finding is quite similar to those reported by Yone and colleagues in Cameroon [16]. The study has shown male gender predominance in all forms of EPTB. A plausible explanation for this slight male gender predilection of EPTB may perhaps be a general trend of males being at an increased risk of TB compared to females as reported in a recent systematic review aimed to critically examine social determinants TB in sub-Saharan Africa by Saidu and colleagues [20] ( Table 3).
Although we would have liked to identify the risk factors for EPTB in our study, our data is limited to already existing variables captured in the TB registers and case records of patients. Data on several clinical co-morbidities, socio-demographic and behavioural risk factors for TB/EPTB were not captured in the TB registers at the DOTS centres. Improved understanding of these risk factors may help clinicians to apply a high index of suspicion to certain high-risk populations as well as enable public health authorities to achieve the goal of preventing TB. Moreover, another limitation in our study is that the National TB register do not capture information on disseminated TB, i.e., TB existing in more than one site. Therefore, several EPTB may have passed for pulmonary TB at the study site, thereby under-reported the actual prevalence of ETPB. In addition not all staff at the DOTS clinic is trained on data entry and record keeping as we have discovered a lot of uncompleted TB register in the course of our study. We therefore suggest that the National Tuberculosis Control Programme of Nigeria improve on its TB register do include relevant information on site as well as risk factors for both PTB and EPTB as well as adequately train the staff at DOTS clinics on data entry and record keeping.